Incidence and Prevalence of Keratoconus Based on Scheimpflug Imaging
Authors: Elsie Chan, Elaine W. Chong, Samantha Sze-Yee Lee, Maria Franchina, Seyhan Yazar, Peter Eastwood, Nigel McArdle, David A. Mackey, Gareth Lingham
Journal: Ophthalmology (2022)

Keratoconus is a disorder characterized by bilateral corneal thinning, with an onset typically in the first 3 decades of life.1Gomes J.A. Tan D. Rapuano C.J. et al.Global consensus on keratoconus and ectatic diseases.Cornea. 2015; 34: 359-369Crossref PubMed Scopus (3) Google Scholar,2Godefrooij D.A. de Wit G.A. Uiterwaal C.S. et al.Age-specific incidence and prevalence of keratoconus: a nationwide registration study.Am J Ophthalmol. 2017; 175: 169-172Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar In this study, we report the prevalence of keratoconus among 28-year-old Generation 2 (Gen2) participants of the Raine Study in Western Australia, the incidence between 20 and 28 years of age, and the risk factors associated with keratoconus. We have previously reported the prevalence of keratoconus at the 20-year follow-up of the Raine Study as 1.2% or 120 cases per 100 000 people.3Chan E. Chong E.W. Lingham G. et al.Prevalence of keratoconus based on Scheimpflug imaging: the Raine study.Ophthalmology. 2021; 128: 515-521Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Previous publications based on national health insurance data include a reported keratoconus prevalence of 265 cases per 100 000 and an annual incidence of 13.3 cases per 100 000 in The Netherlands.2Godefrooij D.A. de Wit G.A. Uiterwaal C.S. et al.Age-specific incidence and prevalence of keratoconus: a nationwide registration study.Am J Ophthalmol. 2017; 175: 169-172Abstract Full Text Full Text PDF PubMed Scopus (292) Google Scholar However, health insurance databases likely underestimate true disease prevalence and incidence. The Raine Study is a multi-generational cohort study based in Perth, Western Australia. The data in this report were collected from the 20-year (conducted 2010–2012) and 28-year (2018–2020) follow-up visits of the Gen2 cohort, when participants underwent an ophthalmic examination, including Scheimpflug imaging (Pentacam, Oculus) and completed a health questionnaire.4Yazar S. Forward H. McKnight C.M. et al.Raine eye health study: design, methodology and baseline prevalence of ophthalmic disease in a birth-cohort study of young adults.Ophthalmic Genet. 2013; 34: 199-208Crossref PubMed Scopus (48) Google Scholar Visual symptoms were not recorded. A full list of ophthalmic and nonophthalmic examinations, questionnaire, and data variables are available online (www.rainestudy.org.au). Differences between active and inactive participants in the Raine Study have been published and are unlikely to have an impact on the results of this study.5Costello L. Dare J. Dontje M. Straker L. Informing retention in longitudinal cohort studies through a social marketing lens: Raine Study Generation 2 participants' perspectives on benefits and barriers to participation.BMC Med Res Methodol. 2020; 20: 202Crossref PubMed Scopus (3) Google Scholar A Belin/Ambrόsio Enhanced Ectasia Display (BAD-D) score of ≥ 2.6 in at least 1 eye was used to define tomographic evidence of keratoconus.6Belin M.W. Khachikian S.S. Ambrosio Jr., R. Salomao M.Q. Keratoconus/Ectasia Detection with the Oculus Pentacam: Belin / Ambrosio Enhanced Ectasia Display.Highl Ophthalmol. 2007; 35: 5-12Google Scholar All scans with a BAD-D ≥ 2.6 were further analyzed by corneal specialists (E.C., E.W.C.) for false-positives. Where both eyes of a participant had BAD-D ≥ 2.6, the eye with the higher score was used for analysis. Potential ocular and nonocular risk factors at the 20-year follow-up were investigated, including the sun exposure–related variables serum 25-hydroxyvitamin D concentration, measured using liquid chromatography tandem mass spectrometry and deseasonalized for month of collection, and total conjunctival ultraviolet autofluorescence (CUVAF) in both eyes. Apnea-hypopnea index (AHI; events/hour), minimum and mean peripheral capillary oxygen desaturation (%), and T90 (time where peripheral capillary oxygen saturation was < 90%) measured at a sleep study performed at the 22-year follow-up were also assessed.7Lee S.S.Y. McArdle N. Sanfilippo P.G. et al.Associations between optic disc measures and obstructive sleep apnea in young adults.Ophthalmology. 2019; 126: 1372-1384Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar The study was conducted in accordance with the tenets of the Declaration of Helsinki. Ethical approval was obtained from the University of Western Australia's Human Research Ethics Committee. All participants provided written informed consent. Figure 1 shows an overview of participants with Scheimpflug imaging data. Of the 755 participants at the 28-year follow-up available for inclusion in the study, 26 participants were diagnosed with keratoconus. The prevalence of keratoconus at the 28-year follow-up was 3.4% or 1 in 30 people. Based on the BAD-D threshold of 2.6 at the 28-year follow-up, compared with those without keratoconus, participants with keratoconus were more likely to be male (69.2% vs. 48.0%, P = 0.045), to have a shorter axial length (22.98 mm vs. 23.70 mm, P < 0.001, IOLMaster V.5; Carl Zeiss Meditec AG), to have poorer visual acuity (0.00 vs. –0.09 logarithm of the minimum angle of resolution, P = 0.002), and to have higher astigmatism (–1.00 diopter [D] vs. –0.50 D, P < 0.001) and myopia (–1.67 D vs. –0.30 D spherical equivalent, P = 0.01) on cycloplegic autorefraction (ARK-510A autorefractor, Nidek, Japan). Additionally, there were significant differences in multiple parameters including keratometric and pachymetric indices on Scheimpflug imaging (Table S1, available at www.aaojournal.org). After excluding 8 participants who were diagnosed with keratoconus at the 20-year follow-up, 669 participants had Scheimpflug imaging data at both the 20- and 28-year follow-up visits (Fig 1) and were available for analysis of keratoconus incidence (representing 52.0% of the 1303 participants who had Scheimpflug imaging at 20 years). Mean follow-up time was 8.3 years (range, 6.6–9.8 years or 5526 person-years). From this group, 15 participants (8 bilateral, 7 unilateral cases) were identified as having new onset of keratoconus. The incidence of keratoconus over the 8-year period was therefore 2.2% (95% confidence interval, 1.12–3.36) or 271 per 100 000 person-years. We did not identify any association between keratoconus and self-reports of allergic diseases (asthma, allergic rhinitis, or ocular allergies) or body mass index. In univariable analysis, we found an association between higher risk of keratoconus and smaller CUVAF area, and higher AHI. In multivariable analysis, after adjusting for age, we found that sex (odds ratio [OR], 3.23, P = 0.048), CUVAF (per 10 mm2 increase, OR, 0.72, P = 0.007), and AHI (per 10 events/hour increase, OR, 2.93, P = 0.001) were significant risk factors for keratoconus. Analysis of AHI by categorizing into no obstructive sleep apnea (OSA) (AHI < 5), mild OSA (AHI 5–14), moderate OSA (AHI 15–29), and severe OSA (AHI ≥ 30)7Lee S.S.Y. McArdle N. Sanfilippo P.G. et al.Associations between optic disc measures and obstructive sleep apnea in young adults.Ophthalmology. 2019; 126: 1372-1384Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar resulted in ORs of 3.16 (P = 0.09), 7.98 (P = 0.02), and 29.25 (P = 0.007), respectively (Tables S2 and S3, available at www.aaojournal.org). The CUVAF area may be a biomarker for long-term ultraviolet exposure that may result in a natural corneal cross-linking, thus reducing the risk of keratoconus. However, arguing against such a relationship is the lack of association between serum 25-hydroxyvitamin D concentration, a short-term measure of sun exposure, and keratoconus. The association between AHI and keratoconus is unlikely due to hypoxia, because associations were not seen with either capillary oxygen saturation or T90. To examine ocular associations for incident keratoconus, we selected parameters that are commonly measured during a standard ocular examination. On univariable analysis, astigmatism, K1, K2 (mean simulated keratometry reading in the flattest and steepest meridian, respectively), central corneal thickness (CTcentral), and axial length were significantly associated with incident keratoconus (Table S4, available at www.aaojournal.org). On multivariable analysis, only steeper K2 and thinner CTcentral remained significant. Although K2 and CTcentral are established features of keratoconus, the Global Delphi Panel of Keratoconus and Ectatic Diseases considered central pachymetry as the least reliable indicator for diagnosing keratoconus.1Gomes J.A. Tan D. Rapuano C.J. et al.Global consensus on keratoconus and ectatic diseases.Cornea. 2015; 34: 359-369Crossref PubMed Scopus (3) Google Scholar Our findings reinforce the value of K2 and CTcentral in assessing both current and future risk of keratoconus in individuals undergoing routine ocular examinations. In a population of young adults in Western Australia, our study reports one of the highest prevalence and incidence of keratoconus in the world. This study emphasizes the importance of early screening for keratoconus in individuals aged 20 to 28 years, especially male individuals and those with steeper K2, higher astigmatism, and thinner corneas and who spend less time outdoors or have sleep apnea. 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